LANL2DZ basis sets recontracted in the framework of density functional theory.
In this paper we report recontracted LANL2DZ basis sets for first-row transition metals. The valence-electron shell basis functions were recontracted using the PWP86 generalized gradient approximation functional and the hybrid B3LYP one. Starting from the original LANL2DZ basis sets a cyclic method was used in order to optimize variationally the contraction coefficients, while the contraction scheme was held fixed at the original one of the LANL2DZ basis functions. The performance of the recontracted basis sets was analyzed by direct comparison between calculated and experimental excitation and ionization energies. Results reported here compared with those obtained using the original basis sets show clearly an improvement in the reproduction of the corresponding experimental gaps.


Biological effect of laser-assisted scar healing (LASH) on standardized human three-dimensional wound healing skin models using fractional non-ablative 1540 nm Er:Glass or 1550 nm diode lasers.
In postoperative wound healing after surgical operations or ablative laser treatments, recent studies suggest the timely use of non-ablative fractional laser treatments with the aim to improve wound healing and prevent pathological scar formation. However, the underlying molecular mechanisms are poorly understood. The aim of this study was to investigate the effects of laser-assisted scar healing (LASH) at the molecular level and to combine it with already established wound healing-promoting local treatments. We irradiated full-thickness 3D skin models with a fractional ablative Er:YAG laser to set standardized lesions to the epidermal and upper dermal layer. Subsequently, LASH was induced by irradiating the models with either a fractional non-ablative 1540 nm Er:Glass or 1550 nm diode laser. In addition, we tested the combination of non-ablative fractional laser treatment and topical aftercare with a dexpanthenol-containing ointment (DCO). Histological analysis revealed that models irradiated with the 1540 nm Er:Glass or 1550 nm diode laser exhibited accelerated but not complete wound closure after 16 h. In contrast, additional topical posttreatment with DCO resulted in complete wound closure. At gene expression level, both non-ablative laser systems showed similar effects on epidermal differentiation and mild anti-inflammatory properties. The additional posttreatment with DCO enhanced the wound-healing effects of LASH, especially the upregulation of epidermal differentiation markers and anti-inflammatory cytokines at the gene expression level. This in vitro study deciphers the biological effects of LASH with a fractional non-ablative 1540 nm Er:Glass or a 1550 nm diode laser in 3D skin models. These data help to better understand the biological properties of the LASH technique and is important to optimize its application.


Diagnosis and management of neutrophilic myeloid neoplasms.
Chronic neutrophilia is commonly seen with persistent infections, inflammatory disorders, smoking, solid tumors, and specific medications. However, after reactive causes have been excluded, a workup for primary (clonal) neutrophilic disorders, such as myeloproliferative neoplasms (MPNs) and myelodysplastic/myeloproliferative overlap syndromes, should be pursued. Except for chronic myeloid leukemia, which is defined by the presence of the Philadelphia (Ph) chromosome, and the classic Ph chromosome-negative MPNs (polycythemia vera, essential thrombocythemia, and primary myelofibrosis), clonal neutrophilic neoplasms historically have been challenging to diagnose and classify. The 2016 revised World Health Organization classification of these disorders has been based mainly on clinicopathologic features. However, recent discoveries of the molecular alterations underlying these disorders have served to supplement our knowledge of their morphologic and clinical features, opening new therapeutic avenues. In this review, we discuss the diagnostic approach, prognostic features, and treatments of neutrophilic myeloid neoplasms, with a focus on chronic neutrophilic leukemia, atypical chronic myeloid leukemia, and chronic myelomonocytic leukemia.


Conjunctival impression cytology in patients wearing contact lenses.
Evaluation of contact lens-induced cytologic changes on the conjunctival surface. Fifty eyes of 25 patients wearing soft or rigid gas-permeable contact lenses, and 50 healthy eyes of 25 control subjects were examined with conjunctival impression cytology. Of the patients wearing contact lenses, 40% did not have any contact lens-related complaints, whereas 60% had some minor complaints related to contact lens intolerance. The material obtained by impression cytology was examined with regard to epithelial cell morphology, goblet cell density, and snake-like nuclear chromatin changes. When epithelial cell morphology was graded according to the system described by Nelson, specimens from the control group revealed 90% of the eyes to be grade 0 and 10% to be grade 1, whereas of the eyes wearing contact lenses, 8% were grade 0, 36% grade 1, 32% grade 2, and 24% grade 3. Thus statistically significant differences were observed between the control group and the contact lens group with regard to each grade (p < 0.05) as well as to the goblet cell densities (p < 0.05). Snake-like chromatin changes, on the other hand, were observed in 30 and 27% of the eyes wearing soft and rigid gas-permeable contact lenses, respectively, whereas these were not encountered in any eye in the control group. Epithelial changes were noted to be more frequent and more severe in symptomatic patients than in those without any complaints. No correlation was found between average duration of contact lens wear and the risk of contact lens intolerance or development of squamous metaplasia.


Anti-Cancer Potential of Phytochemicals: The Regulation of the Epithelial-Mesenchymal Transition.
A biological process called epithelial-mesenchymal transition (EMT) allows epithelial cells to change into mesenchymal cells and acquire some cancer stem cell properties. EMT contributes significantly to the metastasis, invasion, and development of treatment resistance in cancer cells. Current research has demonstrated that phytochemicals are emerging as a potential source of safe and efficient anti-cancer medications. Phytochemicals could disrupt signaling pathways related to malignant cell metastasis and drug resistance by suppressing or reversing the EMT process. In this review, we briefly describe the pathophysiological properties and the molecular mechanisms of EMT in the progression of cancers, then summarize phytochemicals with diverse structures that could block the EMT process in different types of cancer. Hopefully, these will provide some guidance for future research on phytochemicals targeting EMT.


A study of protein side-chain dynamics from new 2H auto-correlation and 13C cross-correlation NMR experiments: application to the N-terminal SH3 domain from drk.
Two new NMR experiments are presented for measuring side-chain dynamics in proteins. The first method, requiring 15N, 13C, approximately 50% 2H-labeled protein, measures 2H T1 and T1p spin relaxation times at side-chain positions. A second experiment permits the straightforward measurement of 13C-1H dipole-dipole cross-correlation relaxation rates at 13C beta positions in 15N, 13C-labeled molecules. An excellent correlation is observed between order parameters, describing the amplitude of motion at these sites, obtained on the basis of 2H relaxation and dipole-dipole cross-correlation relaxation rates. Together these experiments provide a powerful approach for selecting appropriate motional models. The methods are applied to study the side-chain motional properties of the N-terminal SH3 domain from the signaling protein drk.


Daptomycin Exposure as a Risk Factor for Daptomycin-Induced Eosinophilic Pneumonia and Muscular Toxicity.
High-dose daptomycin is increasingly used in patients with bone and joint infection (BJI). This raises concerns about a higher risk of adverse events (AEs), including daptomycin-induced eosinophilic pneumonia (DIEP) and myotoxicity. We aimed to examine pharmacokinetic and other potential determinants of DIEP and myotoxicity in patients with BJI receiving daptomycin. All patients receiving daptomycin for BJI were identified in a prospective cohort study. Cases were matched at a 1:3 ratio, with controls randomly selected from the same cohort. Bayesian estimation of the daptomycin daily area under the concentration-time curve over 24 hours (AUC24h) was performed with the Monolix software based on therapeutic drug monitoring (TDM) data. Demographic and biological data were also collected. Risk factors of AEs were analyzed using Cox proportional hazards model. From 1130 patients followed over 7 years, 9 with DIEP, 26 with myotoxicity, and 106 controls were included in the final analysis. Daptomycin AUC24h, C-reactive protein, and serum protein levels were associated with the risk of AEs. The adjusted hazard ratio of DIEP or myotoxicity was 3.1 (95% confidence interval [CI], 1.48-6.5; P < .001) for daptomycin AUC24h > 939 mg/h/L, 9.8 (95% CI, 3.94-24.5; P < .001) for C-reactive protein > 21.6 mg/L, and 2.4 (95% CI, 1.02-5.65; P = .04) for serum protein <72 g/L. We identified common determinants of DIEP and myotoxicity in patients with BJI. Because the risk of AEs was associated with daptomycin exposure, daptomycin TDM and model-informed precision dosing may help optimize the efficacy and safety of daptomycin treatment in this setting. A target AUC24h range of 666 to 939 mg/h/L is suggested.


Including women in clinical trials: how about the women scientists?
What happens when women scientists are excluded from designing and conducting research? This paper discusses the importance of recruiting and retaining women as scientists. It explores the impact on science of discrimination, harassment, and retaliation against women scientists. The paper presents case examples suggesting that when women scientists' careers are stymied, research that could be beneficial to women may be devalued, delayed, or derailed.


Dielectric study of the interaction between DNA and an oligopeptide (lysine-tyrosine-lysine).
Interaction between Na-DNA and the oligopeptide lysine-tyrosine-lysine (LTL) is studied by a dielectric method. The comparison between conductivities (at the frequence of 5MHz) of LTL alone and of the complex LTL-DNA allows us to show up an electrostatic interaction between LTL and phosphates sites of DNA. During the formation of the complex LTL-DNA, a certain fraction of Na+ counter-ions is ejected from the phosphates sites.


Child and family predictors of relative weight change in a low-income, school-based weight management intervention.
Introduction: Minority and low-income children are underrepresented in school-based weight management programs despite higher risk of obesity and the external contexts that influence their success are largely unknown. This study examines predictors of weight outcomes following the socioecological model in a school-based weight management intervention implemented in an elementary school serving primarily low-income, Black youth. Methods: Children (n = 145; ages 4-9) participated in an 8-month school-based weight management intervention that included components to increase physical activity, promote healthy eating, and engage parents. Children had height and weight measured at baseline and postprogram and parents completed questionnaires at baseline. Socioecological predictors (e.g., child demographic, parent beliefs and attitudes, family and home environment, and social contexts of the family) of zBMI change were assessed using linear regressions. Results: Weight change over the program differed by baseline weight status such that children with obesity lost weight, while children of healthy weight and with overweight gained weight. Children who were younger and had healthier family food choices at baseline were better able to maintain their weight, whereas children from food insecure families gained weight. Discussion: Children of different weight categories from low-income families vary in their response to universally delivered school-based weight management programs. Future work should consider how to address needs of children from different weight classes as well as to effectively target children with risk factors for excessive weight gain (e.g., older, food insecure, less healthful food choices), which may involve broader or more integrative approaches. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Surgical substrates of postoperative junctional ectopic tachycardia in congenital heart defects.
Junctional ectopic tachycardia is a major cause of postoperative morbidity after surgery for congenital cardiac disease. To elucidate the mechanism of junctional ectopic tachycardia, surgical correlations were studied in four types of congenital heart defects involving closure of a ventricular septal defect, relief of right ventricular outflow tract obstruction, or both. Between 1997 and 1999, a total of 343 consecutive patients underwent repair of tetralogy of Fallot (n = 114), common truncus arteriosus (n = 10), ventricular septal defect (n = 161), and atrioventricular septal defect (n = 58). Variables studied included demographic and bypass data, surgical approaches toward ventricular septal defect closure and relief of right ventricular outflow tract obstruction, and resection as opposed to division of muscle bundles. Junctional ectopic tachycardia occurred most frequently after repair of tetralogy of Fallot (n = 25; 21.9%), with no cases occurring after repair of common trunk, 6 occurring after repair of ventricular septal defect (3.7%), and 6 occurring after repair of atrioventricular septal defect (10.3%). Stepwise logistic regression revealed that resection of muscle bundles (P <.0001), higher bypass temperatures (P <.03), and relief of right ventricular outflow tract obstruction through the right atrium (P <.05) significantly and independently predicted postoperative junctional ectopic tachycardia. Relief of right ventricular outflow tract obstruction appears to be more important in the causation of junctional ectopic tachycardia than does ventricular septal defect closure, which may explain the higher incidence of this complication after tetralogy of Fallot repair. Muscular resection seems to be more arrhythmogenic than is simple division. Increased traction through the right atrium for relief of right ventricular outflow tract obstruction would fit the hypothesis that enhanced automaticity of the His bundle, the morphologic substrate for junctional ectopic tachycardia, may result from direct trauma or infiltrative hemorrhage of the conduction system. When feasible, techniques avoiding both extensive muscle resection and excessive traction should be applied during resection of right ventricular outflow tract obstruction.


Haemoptysis secondary to a complicated hydatid cyst of the lung: A case report.
Pulmonary hydatid disease is almost exclusively caused by the infestation of the larval stage of Echinococcus granulosus. Humans are infected, accidentally, through the faeco-oral route by the ingestion of food and milk, contaminated by dog faeces containing the ova of parasites or direct contact with dogs. We describe an unusual cause of massive haemoptysis in a young male who had bilateral lung hydatid cysts as well as a large splenic hydatic cyst. He underwent bilateral thoracotomies for cyst excision for relief of haemoptysis.


Prevalence of Temporomandibular Dysfunction and its Association with Malocclusion in Children: An Epidemiologic Study.
Malocclusion is one etiological factor of temporomandibular joint disorder (TMD). This study investigates the prevalence of TMD and the relationship between TMD and the type of occlusion. A sample of 923 children (463 girls and 460 boys, ages 7-12 years old) was grouped not only by chronological age but also by gender. The information was collected on functional occlusion (anterior and lateral sliding, interferences), dental wear, mandibular mobility (maximal opening, deflection, deviation), and temporomandibular joint and muscular pain recorded by palpation. Headache was the only symptom of temporomandibular dysfunction (TMD) reported by the children. The results showed that one or more clinical signs were recorded in 25% of the subjects, most of which were mild in character. The prevalence increased during the developmental stages. Girls were in general more affected than boys. In this study, many subjects with TMD had malocclusions. Early treatment may be important in the prevention of severe TMD. Significant associations were found between different signs, and TMD was associated with posterior crossbite, anterior open bite, Angle Class II and III malocclusions, and extreme maxillary overjet.


Visual performance and photic disturbances with diffractive and non-diffractive EDOF intraocular lenses using minimonovision: A randomized trial.
To compare visual performance and photic visual disturbances of patients implanted with two different extended depth of focus (EDOF) intraocular lenses using mini-monovision. Ambulatory surgical center at the University of São Paulo in Ribeirão Preto, Brazil. Prospective, examiner-masked, randomized clinical trial. Subjects were assigned to either bilateral Symfony (SYM) or Vivity (VIV) implant, with one eye targeted for myopia (-0.75 D). Defocus curve, contrast sensitivity (Pelli-Robson), patient-reported spectacle independence questionnaire (PRSIQ), and a quality of Vision (QoV) questionnaire were recorded at 3 months after surgeries. A total of 126 patients finished the follow-up: group SYM: 60 and VIV: n=66. Regarding near visual acuity, 80% of patients in the SYM group and 84% of patients in the VIV group achieved J2 or better on near planned eye (P = 0.3840). No significant differences were found between groups for distance visual acuity, defocus profiles, PRISC, contrast sensitivity, or reading speed (P>0.05). Notably, significant between-group differences were observed for bothersome visual disturbances (P = 0.0235), with 45% of patients in the SYM group with a score of 0 (zero) for bothersome, compared to 66% in the SYM group. Mini-monovision using these EDOF lenses was well-tolerated in the patient cohort. No significant differences were found for visual performance tests between VIV and SYM groups. However, the data suggest that Vivity is associated with a lower probability of bothersome visual disturbances compared to Symfony.


Successive positron emission tomography measurement of cerebral blood flow and neuroreceptors in the human brain: an 11C-SA4503 study.
For evaluating a newly developed radioligand for positron emission tomography (PET), successive measurements of regional cerebral blood flow (rCBF) and the kinetics of the radioligand in the same subject are preferable in the first clinical trial. In this study, we demonstrate an example for the study of (11)C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylprophyl) piperazine ((11)C-SA4503) for mapping sigma(1) receptors in the human brain. Five healthy male subjects underwent two successive PET scans with (15)O-H(2)O to measure the rCBF and with (11)C-SA4503 (dynamic 60-min scan). The brain kinetics of (11)C-SA4503 was evaluated using the time-activity curve (TAC) of tissue in each of the 11 regions of the brain and the metabolite-corrected TAC of plasma on the basis of a two-tissue compartment fourparameter model. The estimated parameters were four rate constants: K (1), influx from plasma to brain tissue; k (2), efflux from tissue to plasma; k (3), association between tracer and receptors; and k (4), dissociation of tracer-receptor complex, and the binding potential (BP), k (3)/k (4). (11)CSA4503 was distributed all over the brain, and the TACs exhibited an accumulation pattern in all the 11 regions. K (1) of (11)C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did not. The regional difference in the BP of (11)C-SA4503 is compatible with those of sigma(1) receptors. In conclusion, successive PET measurements of rCBF and the brain kinetics of radioligand-neuroreceptor binding are useful for the first clinical trial of a newly developed radioligand for mapping neuroreceptors, and the protocol is applicable to pathophysiological studies of brain disorders.


[Familial spam (streptococcal pharyngitis associated myocarditis): is it a new entity or a coincidence?].
Myocarditis is an inflammation of the myocardium. It is potentially life-threatening, with a wide range of clinical presentations and most often it is caused by various viral, bacterial or fungal infections. A 27 year-old man, previously hospitalized due to streptococcal tonsillitis, was admitted to ED because of chest pain. He presented with pain, tightness irradiating to both shoulders and arms and associated sweating and vomiting. The ECG revealed ST elevations on Leads: V5-V6, V7-V9, II, III, AVF and ST depressions on Leads V1-V3. Laboratory results showed elevated Liver enzymes, and positive troponin-5.766 ng/mL The patient showed clinical improvement with NSAIDs and was diagnosed with myocarditis. His brother was admitted to the hospital a year earlier with a sore throat accompanied by chest pain and was diagnosed with perimyocarditis. The family history of myocarditis after a streptococcal infection, affecting two brothers a year apart from each other, raises the possibility that there is a genetic component responsible for an individuaLs susceptibility to develop myocarditis.


Influence of the cell interaction parameters on the simulated CD4+ lymphocyte depletion in HIV infection.
The previously suggested mathematical models of CD4+ lymphocyte depletion in HIV-infected individuals are analysed from the point of view of fundamental cell interaction mechanisms involved. Under the assumption of growth restriction of the HIV by cytotoxic lymphocytes, the intensity of the feedback mechanism increasing the influx of immature CD4+ lymphocytes and the intensity of the helper effect of CD4+ lymphocytes during the maturation of cytotoxic cells are evaluated and compared in a wide range of the respective model parameters. In this respect also the role of the proliferation rate of these cytotoxic lymphocytes under antigenic stimulation by HIV products is discussed. In addition, an alternative elimination mechanism of CD4+ lymphocytes is investigated, which assumes their destruction by cytotoxic lymphocytes. It is concluded that any of the considered cases of the influx amplification parameter, helper effect intensity parameter, and CD4+ lymphocyte elimination mechanism can be used for a qualitative adjustment of the model to clinical data.


Pattern of presentation of idiopathic polypoidal choroidal vasculopathy in Ibadan, Sub-Saharan Africa.
Idiopathic polypoidal choroidal vasculopathy is an abnormal choroidal vascular pathology similar to age-related macular degeneration. It may present with sudden visual loss from hemorrhagic retinal pigment epithelial detachment and breakthrough vitreous hemorrhage or with chronic recurrent episodes. The condition is not uncommon in the retina clinic at the University College Hospital, Ibadan, Sub-Saharan Africa. This study presents the pattern of presentation in Ibadan. We review all cases of idiopathic polypoidal choroidal vasculopathy seen from 2007 to 2012 in the retina clinic at the University College Hospital, Ibadan, to determine the major pattern of presentations, available treatment modalities, and visual outcomes. Ten cases were seen during the study period. Their mean age was 58 years, with a male to female ratio of 1:4. The most common presenting complaint was sudden visual loss. Major examination findings were retinal pigment epithelial detachment, orange subretinal lesions, and breakthrough vitreous hemorrhage. The modalities of treatment available included vitrectomy to clear vitreous hemorrhage. Intravitreal bevacizumab reduced the height of the pigment epithelial detachment and cleared vitreous hemorrhage. Thermal laser was applied for extrafoveal lesions. Two patients with subfoveal lesions were referred abroad for photodynamic therapy. Visual outcome showed significant improvement in vitrectomized patients who presented with vitreous hemorrhage. Presenting vision of hand motion and light perception improved to vision ranging from counting fingers to 6/12 after vitrectomy. Idiopathic polypoidal choroidal vasculopathy may not be uncommon in Sub-Saharan Africa. A high index of suspicion is warranted in the diagnosis so as to provide timely intervention.


Long-range hole migration in irradiated crystals of nucleic acid bases. An EPR study.
Polycrystalline samples of several nucleic acid bases co-crystallized with small amounts of thioanalogues as impurities were X-irradiated at 77 K and investigated by electron paramagnetic resonance (EPR) spectroscopy for sulphur (S)-centered radicals. Anhydrous cytosine, cytosine monohydrate and cytosine hydrochloride with 0.01-1% incorporated thiocytosine gave strong EPR signals characteristic of S-centered radicals, with spectroscopic parameters different from those for irradiated thiocytosine alone. Likewise, in guanine hydrochloride doped with thioguanine (0.1-1%), strong signals of the radicals associated with thioguanine were observed. For the thymine-thiothymine systems (anhydrous and monohydrate) no characteristic S-centered radicals were observed after the same treatment. This was also the case for samples from non-matching bases and thiols (e.g. cytosine-thioguanine or guanine-thiocytosine), for combinations in the form of frozen glasses or frozen aqueous solutions and for almost all freeze-dried samples composed of the bases containing a small amount of thioanalogues. These observations are discussed in terms of the long-range migration of holes within the stacked base systems.


Prognostic impact of insulin-like growth factor-I and its binding proteins, insulin-like growth factor-I binding protein-2 and -3, on adverse histopathological features and survival outcomes after radical cystectomy.
Insulin-like growth factor-I and its binding proteins are involved in cancer development, progression, and metastasis. In urothelial carcinoma, the impact of this pathway is still poorly investigated. The present large cohort study aimed to evaluate the association of preoperative circulating levels of insulin-like growth factor-I, insulin-like growth factor-I binding protein-2 and -3 on outcomes after radical cystectomy. A retrospective cohort study of the plasma specimens from 1036 consecutive urothelial carcinoma patients who were treated with radical cystectomy. The primary and secondary outcomes were adverse histopathological features and survival outcomes. Binominal logistic regression and multivariable Cox regression analyses were performed to assess the association of plasma levels of insulin-like growth factor-I, insulin-like growth factor-I binding protein-2 and -3 with outcomes. On multivariable analysis adjusting for the effects of preoperative variables, lower insulin-like growth factor-I binding protein-2 levels were associated with an increased risk of lymph node metastasis and (any non-organ confined disease) any non-organ confined disease. Insulin-like growth factor-I binding protein-3 levels were also inversely independently associated with lymph node metastasis. Receiver operating characteristic curve analysis showed that the addition of insulin-like growth factor-I binding proteins biomarkers to a reference model significantly improved the discriminating ability for the prediction of lymph node metastasis (+10.0%, P < 0.001). On multivariable Cox regression models, lower levels of both insulin-like growth factor-I binding protein-2 and -3 plasma levels were associated with recurrence-free survival, cancer-specific survival, and overall survival. insulin-like growth factor-I binding protein-2 and -3 levels and improved the discrimination of a standard reference model for the prediction of recurrence-free survival, cancer-specific survival, and overall survival (+4.9%, 4.9%, 2.3%, respectively). Preoperative insulin-like growth factor-I binding protein-2 and -3 are significantly associated with features of biologically and clinically aggressive urothelial carcinoma. These biomarkers improved prognostic urothelial carcinoma models.


Reproducibility of cerebrovascular reactivity measures in children using BOLD MRI.
To evaluate the reproducibility of cerebrovascular reactivity (CVR) measurements acquired in children using magnetic resonance imaging (MRI) in combination with a computer-controlled carbon dioxide (CO2 ) stimulus. Ten healthy children (age 16.1 ± 1.6 years) underwent CVR imaging on a 3T scanner using a blood-oxygen level-dependent (BOLD) MRI sequence. Targeted hypercapnia was induced during imaging with a CO2 gas challenge delivered using a specialized gas sequencer (RespirAct). A total of four BOLD scans were performed over 2 separate days to test within-day and between-day consistency of the data. CVR values were computed by correlating the relative change in BOLD signal in response to the CO2 stimulus delivered to the each subject. Intraclass correlation coefficients (ICCs) of within-day values show highly reproducible measures in both the gray matter (ICC = 0.857, P < 0.001) and white matter (ICC = 0.895, P < 0.001). Relatively lower between-day reproducibility was observed in both the gray matter (ICC = 0.776, P = 0.001) and white matter (ICC = 0.719, P = 0.004). Using a computer-controlled CO2 stimulus, we have demonstrated the reliability of BOLD-CVR measurements in pediatric subjects. Within-day and between-day metrics of reproducibility were comparable to adult data.


Simultaneous diagnosis and treatment of bilateral breast carcinoma and endometrial adenocarcinoma. Implications for screening.
The association of breast and endometrial carcinoma has been demonstrated by many studies. Most of the cases are related to the previous use of tamoxifen for the treatment of breast carcinoma. However, triple primary malignancies on the same individual are very rare. This is an unusual case regarding simultaneous diagnosis and treatment of bilateral breast carcinoma and endometrial adenocarcinoma. The clinical aspects and treatment of this unique case are presented.


Survival and disease-progression benefits with treatment regimens for advanced colorectal cancer: a meta-analysis.
Many randomised trials have compared different systemic treatment regimens in patients with advanced colorectal cancer. While survival advances have apparently been achieved, the magnitude of these incremental benefits across diverse regimens is less clear. The aim of our study was to estimate the magnitude of survival and disease progression benefits with the use of different regimens in patients with advanced colorectal cancer. We systematically reviewed randomised trials comparing systemic treatment regimens in advanced colorectal cancer. Treatment was categorised by use of or no use of fluorouracil-based regimens, irinotecan, oxaliplatin, bevacizumab, and cetuximab. We used multiple-treatment meta-analysis methodology to combine information from direct comparisons (ie, treatments compared within a randomised trial) and indirect comparisons (ie, treatments compared between trials by combining results on how effective they are against a common comparator treatment) of different chemotherapy regimens. The primary endpoint was death and the secondary endpoint was disease progression. Monte Carlo simulations were used to establish which regimen offered the most benefit for these endpoints. We did analyses of all trials and analysed separately trials that studied first-line treatments and non-first-line treatments. 242 trials published in 1967-2007 (N=56 677 patients) involved 137 different chemotherapy regimens. 37 of these trials were eligible for the multiple-treatment meta-analysis, according to our categorisation, including 47 comparisons of data on death (N=13 875 patients) and 48 comparisons of data on disease progression (N=15 158 patients). Compared with fluorouracil plus leucovorin alone, the risk of death was most decreased with the addition of irinotecan plus bevacizumab (hazard ratio [HR] 0.60, 95% credibility intervals (CrI) 0.44-0.84) and considerable benefits were also noted with addition of irinotecan plus oxaliplatin (HR 0.72 [95% CrI 0.54-0.97]); oxaliplatin plus bevacizumab (HR 0.72 [0.57-0.90]); bevacizumab alone (HR 0.78 [0.60-1.03]); and oxaliplatin alone (HR 0.87 [0.78-0.98]). The disease progression benefits were even more prominent for the addition of irinotecan plus bevacizumab (HR 0.41 [0.28-0.60]); irinotecan plus oxaliplatin (0.53 [0.38-0.73]); oxaliplatin plus bevacizumab (0.46 [0.34-0.61]); bevacizumab alone (0.56 [0.41-0.76]); oxaliplatin alone (0.64 [0.56-0.73]); irinotecan plus cetuximab (HR 0.62 [0.42-0.92]); and irinotecan alone (HR 0.73 [0.65-0.82]). Findings were similar for first-line and non-first-line treatment analyses although data were sparse for non-first-line treatment analyses. Compared with a patient with an anticipated 1-year survival who is treated with fluorouracil and leucovorin, the absolute survival benefit is estimated at 8 months' prolongation with addition of irinotecan plus bevacizumab, 4.7 months' prolongation with addition of oxaliplatin plus bevacizumab or irinotecan plus oxaliplatin, and 1-1.8 months' prolongation with addition of irinotecan alone or oxaliplatin alone. Distinct incremental benefits are noted for diverse chemotherapy regimens in patients with advanced colorectal cancer, with more prominent effects on disease progression than on death. More data are needed at least for the newest drugs to estimate more accurately the magnitude of the benefit derived from their use.


A 7872 cDNA microarray and its use in bovine functional genomics.
The strategy used to create and annotate a 7872 cDNA microarray from cattle placenta and spleen cDNA sequences is described. This microarray contains approximately 6300 unique genes, as determined by BLASTN and TBLASTX similarity search against the human and mouse UniGene and draft human genome sequence databases (build 34). Sequences on the array were annotated with gene ontology (GO) terms, thereby facilitating data analysis and interpretation. A total of 3244 genes were annotated with GO terms. The array is rich in sequences encoding transcription factors, signal transducers and cell cycle regulators. Current research being conducted with this array is described, and an overview of planned improvements in our microarray platform for cattle functional genomics is presented.


Effect of combined fenthion and cimetidine use in rats on lethality, blood cholinesterase activities, and serum cholinesterase isoenzymes.
H2-receptor antagonists inhibit cholinesterase (ChE) activity. We examined perturbations in ChE isoenzyme patterns and ChE activities of rats from the combined effects of fenthion (FEN) and cimetidine (CIM). Sixty-four female Sprague-Dawley rats were divided into 8 groups. Four rat groups were given FEN or gum arabic solution and each group divided into 2 small groups according to the CIM or gum arabic administration. FEN was administered po at 12.3 mg/kg (1/20 LD50) or 24.5 mg/kg (1/10 LD50) for 14 days or 49 mg/kg (1/5 LD50) every 4 days. CIM was given po at 1,500 mg/kg from days 7 to 13. Samples were collected 3 h after CIM administration on days 8 and 13. CIM did not influence ChE isoenzyme patterns or ChE activity. FEN inhibited both the ChE isoenzyme patterns and ChE activities without producing clinical signs. Although 1 rat in the 12.5 mg FEN/kg + CIM group died on day 10, all rats in other FEN (24.5 mg/kg or 49 mg/kg) + CIM groups died on days 8-10. Differences in suppression of ChE isoenzyme patterns were detectable between the FEN-dosed and FEN + CIM-dosed groups. There were no differences in ChE activities between the FEN-dosed and FEN + CIM-dosed groups. The i.p. administration of 500 mg CIM/kg (LD50) did not suppress ChE activities.


Protective effect of vitamin E on cypermethrin-induced follicular atresia in rat ovary: Evidence for energy dependent mechanism.
It has been shown that chronic exposure to cypermethrin (CPM), a pyrethroid pesticide, results in follicular atresia via pathologically affecting angiogenesis, disrupting endocrine potential and enhancing oxidative stress. This study was aimed to uncover the CPM-exposed energy dependent follicular cells apoptosis and to estimate protective effect of vitamin E (VitE) as a potent antioxidant. Thirty six Wistar rats were divided into six groups (n = 6 rats for each group) including; control-sham, CPM-received (CPM, 75 mg kg(-1), intraperitoneally), and CPM and VitE-treated (VitE, 150 mg kg(-1), orally) for 14 and 24 days. The protein biosynthesis of glucose transporter-1 (GLUT-1) and caspase-3 in follicles were estimated by using immuno-histochemical staining at preantral and antral stages. Moreover, the periodic acid Schiff (PAS) staining was performed in order to evaluate the intracytoplasmic carbohydrate ratio in follicular cells and oocyte. Percentages of follicles with GLUT-1, Caspase-3 and PAS-positive cells were compared between groups. Immunohistochemical analyses showed that, VitE significantly up-regulated the GLUT-1 expression and improved the intracytoplasmic carbohydrate supplementation especially at preantral follicles. The cross sections from the CPM-exposed ovaries represented remarkable elevation in percentage of atretic preantral and antral follicles with caspase-3 biosynthesis, which was remarkably (p < 0.05) diminished in VitE co-treated groups. In conclusion, our data showed that VitE by up-regulating of the GLUT-1 biosynthesis improved glucose uptake at follicular cells and oocyte levels that in turn inhibited pro-apoptotic protein caspase-3 biosynthesis.


A field study on the dynamic uptake and transfer of heavy metals in Chinese cabbage and radish in weak alkaline soils.
Vegetables and crops can take up heavy metals when grown on polluted lands. The concentrations and dynamic uptake of heavy metals vary at different growth points for different vegetables. In order to assess the safe consumption of vegetables in weak alkaline farmlands, Chinese cabbage and radish were planted on the farmlands of Baiyin (polluted site) and Liujiaxia (relatively unpolluted site). Firstly, the growth processes of two vegetables were recorded. The growth curves of the two vegetables observed a slow growth at the beginning, an exponential growth period, and a plateau towards the end. Maximum concentrations of copper (Cu), zinc (Zn), lead (Pb), and cadmium (Cd) were presented at the slow growth period and showed a downtrend except the radish shoot. The concentrations of heavy metals (Cu, Zn, and Cd) in vegetables of Baiyin were higher than those of Liujiaxia. In the meanwhile, the uptake contents continued to increase during the growth or halted at maximum at a certain stage. The maximum uptake rates were found on the maturity except for the shoot of radish which took place at the exponential growth stages of root. The sigmoid model could simulate the dynamic processes of growth and heavy metals uptake of Chinese cabbage and radish. Conclusively, heavy metals have higher bioaccumulation tendency for roots in Chinese cabbage and for shoots in radish.


Can Elective Spine Surgery Be Performed Safely Among Nonagenarians?: Analysis of a National Inpatient Database in Japan.
Retrospective cohort study. To compare morbidity and mortality between nonagenarians and other older adult patients who underwent elective spine surgery. There is a lack of information of the perioperative risks of nonagenarians undergoing spine surgery. Data of patients aged ≥65 years who underwent elective spine surgery from July 2010 to March 2013 were extracted from the Diagnosis Procedure Combination database, a nationwide administrative inpatient database in Japan. Clinical outcomes included mortality, occurrence of major complications (cardiac events, respiratory complications, pulmonary embolism, stroke, and acute renal failure), urinary tract infection, and postoperative delirium. These clinical outcomes in nonagenarians were compared with those in patients aged 65 to 79 years and octogenarians. A multivariate logistic regression model fitted with a generalized estimation equation was used to evaluate the influence of advanced age on 90-day mortality and postoperative major complications. Of 88,370 patients identified in the database, 418 were nonagenarians. Compared with patients aged 65 to 79 years and octogenarians, nonagenarians had the highest rates of 90-day mortality (0.2%, 0.3%, and 1.7%, respectively; P < 0.001) and at least one major complication (3.7%, 5.0%, and 7.4%, respectively; P < 0.001). Nonagenarians had the highest proportions of cardiac events, respiratory complications, urinary tract infections, and delirium. The multivariable logistic regression analyses revealed that nonagenarians had increased risks of both 90-day mortality (odds ratio, 8.65; 95% confidence interval, 3.62-20.6) and postoperative major complications (odds ratio, 2.32; 95% confidence interval, 1.61-3.36) compared with patients aged 65 to 79 years. Nonagenarians had increased morbidity and mortality following elective spine surgery compared with other older adult patients. Among the complications, cardiac events, respiratory complications, urinary tract infection, and delirium were more likely to occur in nonagenarians. 3.


The circadian rhythm: an influential soundtrack in the diabetes story.
Type 2 Diabetes Mellitus (T2DM) has been the main category of metabolic diseases in recent years due to changes in lifestyle and environmental conditions such as diet and physical activity. On the other hand, the circadian rhythm is one of the most significant biological pathways in humans and other mammals, which is affected by light, sleep, and human activity. However, this cycle is controlled via complicated cellular pathways with feedback loops. It is widely known that changes in the circadian rhythm can alter some metabolic pathways of body cells and could affect the treatment process, particularly for metabolic diseases like T2DM. The aim of this study is to explore the importance of the circadian rhythm in the occurrence of T2DM via reviewing the metabolic pathways involved, their relationship with the circadian rhythm from two perspectives, lifestyle and molecular pathways, and their effect on T2DM pathophysiology. These impacts have been demonstrated in a variety of studies and led to the development of approaches such as time-restricted feeding, chronotherapy (time-specific therapies), and circadian molecule stabilizers.


Hepatitis E: Update on Prevention and Control.
Hepatitis E virus (HEV) is a common etiology of acute viral hepatitis worldwide. Recombinant HEV vaccines have been developed, but only one is commercially available and licensed in China since 2011. Epidemiological studies have identified genotype 3 as the major cause of chronic infection in immunocompromised individuals. Ribavirin has been shown to be effective as a monotherapy to induce HEV clearance in chronic patients who have undergone solid organ transplant (SOT) under immunosuppressive therapy. Efforts and improvements in prevention and control have been made to reduce the instances of acute and chronic hepatitis E in endemic and nonendemic countries. However, this review shows that further studies are required to demonstrate the importance of preventive vaccination and treatment worldwide, with emphasis on hepatitis E infection in the public health system.


A method to ensure the accuracy of estimates of anaerobic capacity derived using the critical power concept.
Estimates of anaerobic work capacity (AWC) were determined in 26 subjects using the critical power concept. AWC estimates were derived using three mathematically equivalent models: nonlinear power-time, linear power-1/time, and linear work-time. We hypothesized that large variability between estimates generated using the three models might reflect systematic error in the data and that large standard errors of estimate (SEE) might reflect random error. Therefore, subjects were grouped according to the variability in the three AWC estimates and according to the magnitude of the SEE of the parameter estimates. Then AWC estimates were compared to a criterion measure of anaerobic capacity, namely maximal oxygen deficit. When variability in the AWC estimates was low (< 10%), all provided accurate measures of oxygen deficit; also, when SEE were low, estimates were accurate. When variability was high, mean AWC estimates derived using linear models differed from oxygen deficit by over 15%; when SEE were high, mean AWC estimates derived using all models differed from oxygen deficit by over 10%. It is concluded that the accuracy of estimates of anaerobic capacity derived using the critical power concept can best be ensured by accepting values only when all three models provide the same value and/or when the SEE of the AWC estimate is small.


[Cu2+ biosorption by bacterial alginate extracted from aerobic granules and its mechanism investigation].
The biosorption characteristic of copper ions onto dried Ca-alginate made of bacterial alginate extracted from aerobic granules was investigated in batch system. The biosorption rate of Cu2+ onto the alginate, effects of pH and alginate dosage on Cu2+ biosorption capacity and adsorption isotherm were analyzed. The biosorption of Cu2+ onto the dried Ca-alginate was a rapid process. The maximum Cu2+ uptake was 67.67 mg/g at pH 4, initial Cu2+ concentration of 100 mg/L, dried Ca-alginate dosage 0.7 g/L. Accumulation of Cu2+ followed Langmuir and Freundlich adsorption isotherm. Cu2+ adsorption was accompanied by Ca2+ releasing from the dried Ca-alginate and H+ uptake, indicating that the ion exchange between Cu2+ and Ca2+ requires H+ for charge balance. FT-IR secondary derivative spectra and atomic force microscopy analysis gave proof that, the reaction of MG blocks in dried Ca-alginate with Cu2+ and Ca+ were different. Cu2+ may form complex with MG blocks, leading to a much more ordered structure on the surface of the dried Ca-alginate. The dried Ca-alginate bio-adsorbent was regenerated by 100 mmol/L HCI with 91% Cu2+ recovery.


Ultrasound image segmentation and tissue characterization.
Ultrasound image segmentation deals with delineating the boundaries of structures, as a step towards semi-automated or fully automated measurement of dimensions or for characterizing tissue regions. Ultrasound tissue characterization (UTC) is driven by knowledge of the physics of ultrasound and its interactions with biological tissue, and has traditionally used signal modelling and analysis to characterize and differentiate between healthy and diseased tissue. Thus, both aim to enhance the capabilities of ultrasound as a quantitative tool in clinical medicine, and the two end goals can be the same, namely to characterize the health of tissue. This article reviews both research topics, and finds that the two fields are becoming more tightly coupled, even though there are key challenges to overcome in each area, influenced by factors such as more open software-based ultrasound system architectures, increased computational power, and advances in imaging transducer design.


Distribution of angiotensin converting enzyme in sheep hypothalamus and medulla oblongata visualized by in vitro autoradiography.
In vitro autoradiographic mapping of angiotensin converting enzyme (ACE) in sheep brain using the specific ACE inhibitor, 125I-351A, revealed very high densities of binding in large blood vessels and choroid plexus. In the a very high density of labelling occurred in the organum vasculosum of the lamina terminalis and median eminence and a high density in the subfornical organ and moderate density in supraoptic, suprachiasmatic, arcuate and paraventricular nuclei. All fiber tracts were unlabelled. In the medulla oblongata, a very high density of binding was detected in the area postrema and a high density in the nucleus of the solitary tract and dorsal motor nucleus of the vagus; a moderate density was found in the substantia gelatinosa of the spinal tract and the inferior olivary nucleus.


Activity of rifabutin alone or in combination with clofazimine or ethambutol or both against acute and chronic experimental Mycobacterium intracellulare infections.
Rifabutin (ansamycin LM 427) when given alone in doses of 5, 10, or 20 mg/kg showed limited in vivo activity against acute or chronic Mycobacterium intracellulare infections studied in beige C57B1/6, or S/W mice. Prophylactic studies in S/W mice in which chemotherapy was given for 3 wk prior to challenge showed slight improvement. Combination chemotherapy consisting of rifabutin (10 mg/kg) and clofazimine (20 mg/kg) achieved complete sterilization of M. intracellulare infections in spleen and lung when initiated immediately after challenge. Inclusion of ethambutol did not offer additional benefit. If chemotherapy is initiated 3 wk after challenge (established infections), the activity of this double drug combination is less effective.


Exploring Protein-Nanoparticle Interactions with Coarse-Grained Protein Folding Models.
Understanding the fundamental biophysics behind protein-nanoparticle (NP) interactions is essential for the design and engineering bio-NP systems. The authors describe the development of a coarse-grained protein-NP model that utilizes a structure centric protein model. A key feature of the protein-NP model is the quantitative inclusion of the hydrophobic character of residues in the protein and their interactions with the NP surface. In addition, the curvature of the NP is taken into account, capturing the protein behavior on NPs of different size. The authors evaluate this model by comparison with experimental results for structure and adsorption of a model protein interacting with an NP. It is demonstrated that the simulation results recapitulate the structure of the small α/β protein GB1 on the NP for data from circular dichroism and fluorescence spectroscopy. In addition, the calculated protein adsorption free energy agrees well with the experimental value. The authors predict the dependence of protein folding on the NP size, surface chemistry, and temperature. The model has the potential to guide NP design efforts by predicting protein behavior on NP surfaces with various chemical properties and curvatures.


Chlorinated dibenzo-p-dioxin and dibenzofuran congener and homologue distributions in tree bark from Sauget, Illinois, U.S.
Polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) are ubiquitous urban/industrial contaminants found in tree bark, which acts as a long-term passive atmospheric sampler. Twenty seven bark samples (tree age 8–92 years) were collected from residential and industrial areas near Sauget, IL to identify the trends of 2,3,7,8-Cl PCDD & PCDF congener distributions, toxic equivalents (TEQ), and PCDD & PCDF homologue distributions. The Sauget area is heavily industrialized, with a long history of chlorine production, and is the largest single contributor to air pollution exposure risk in St. Louis. Analysis of seven 2,3,7,8 Cl-substituted PCDD and 10 PCDF congeners showed ∑PCDD7 ranging from 2214 to 71821 pg g(–1) lipid and ∑PCDF10 from 355 to 13707 pg g(–1) lipid, the highest in trees <20 years old in both cases. OctaCCD and octaCDF respectively dominated ∑PCDD7 (89% average) and ∑PCDF10 (57% average). The 2,3,7,8-Cl congener profiles showed slight differences among samples showing that all were affected by similar sources but at different magnitudes. ∑TEQ ranged from 35 to 624 pg g(–1) lipid, dominated by 1,2,3,7,8-PeCDD (average = 41.3% of total TEQ). Tetra-Cl through hepta-Cl homologues were dominated by non-2,3,7,8-Cl compounds for both CDD and CDF. Homologue profiles for 26 samples had a "sink" profile dominated by octaCDD, whereas one sample showed effects of a local source.


Asymmetrical, transitional, lumbosacral vertebral segments in six dogs: a characteristic spinal syndrome.
Clinical findings in six dogs with asymmetrical, transitional, lumbosacral vertebral segments are reported. All dogs exhibited low back pain and varying degrees of asymmetrical cauda equina dysfunction. Results of myelography, epidurography, and magnetic resonance imaging (MRI) indicated a unilateral disk protrusion in all dogs. In the dogs with MRIs, focal degenerative alterations in the vertebral end plates and adjacent body of the vertebra were detected. All dogs were treated with a dorsal laminectomy or hemilaminectomy. Results following surgery were good or excellent in all six dogs.


Desmoid tumour biology in patients with familial adenomatous polyposis coli.
Familial adenomatous polyposis (FAP) is caused by mutations in the adenomatous polyposis coli (APC) gene. Desmoid tumours affect up to 26 per cent of patients and contribute significantly to death. This study aimed to assess the influence of sex and mutation site on desmoid tumour development and sex-specific genetic differences in patients with FAP with and without desmoid tumours. Patients with FAP-associated desmoid tumours recorded in the Heidelberg Polyposis Register between 1991 and 2010 were identified. These patients were analysed with respect to clinical parameters and possible risk factors. Some 105 patients with FAP-associated desmoid tumours of a total of 585 patients with FAP were analysed. Male patients had a significantly greater number of desmoid tumours and a larger tumour mass, although tumours were more common in female patients. Desmoid tumours in male patients were located more often in the abdominal wall. Seventy-nine (75.2 per cent) of the 105 patients demonstrated a clear temporal association between a previous operation and subsequent desmoid tumour development; most of these patients were female. Mutation sites in male patients were limited to exons 5, 14 and 15, whereas female patients carried mutations along the entire coding region of the APC gene. Twenty-one per cent of patients with desmoid tumours carried mutations within the 'desmoid region', compared with only 4.1 per cent of the control group without desmoids. There are significant sex differences concerning desmoid tumour manifestation. Female patients appear to have a higher risk of desmoid tumour occurrence independent of the mutation site, whereas in male patients the mutation site seems to exert more influence.


Relativistic Quantum Dynamics of Twisted Electron Beams in Arbitrary Electric and Magnetic Fields.
Relativistic quantum dynamics of twisted (vortex) Dirac particles in arbitrary electric and magnetic fields are constructed for the first time. This allows us to change the controversial contemporary situation when the nonrelativistic approximation is used for relativistic twisted electrons. The relativistic Hamiltonian and equations of motion in the Foldy-Wouthuysen representation are derived. A critical experiment for a verification of the results obtained is proposed. The new important effect of a radiative orbital polarization of a twisted electron beam in a magnetic field resulting in a nonzero average projection of the intrinsic orbital angular momentum on the field direction is predicted.


Species identification of coagulase-negative staphylococcal isolates from blood cultures.
Coagulase-negative staphylococci generally are not fully identified, are called Staphylococcus epidermidis, and are considered contaminants when isolated from blood cultures. In a cancer hospital during 6 months, 46 patients had multiple blood cultures (mean, 3.1) which yielded coagulase-negative staphylococci. Species identification of these showed that 10 of the 46 (22%) were not S. epidermidis. Similarly, 96 coagulase-negative staphylococci isolated from only one of multiple blood cultures from patients and thought to be skin contaminants were identified. Of 96 of the staphylococci, 14 (16%) of the latter group were not S. epidermidis. Species found included S. haemolyticus, S. hominis, S. warneri, S. simulans, and S. xylosus. Eight isolates of these species were methicillin resistant, and all eight were mannitol fermenters. The results suggest that these species invasively infect cancer patients with the same frequency at which the species colonize. No one species was identified as being more pathogenic than the others. Routine species identification of coagulase-negative staphylococci from blood cultures of cancer patients contributed little to management except to occasionally distinguish multiple-episode culture contamination by different species from sustained bacteremia with the same species.


PHOTODYNAMIC THERAPY-INDUCED ACUTE EXUDATIVE MACULOPATHY: Incidence, Clinical Features, and Long-Term Outcomes.
To describe the incidence, clinical features, and long-term outcomes of photodynamic therapy (PDT)-induced acute exudative maculopathy (PAEM) in patients who underwent PDT for various indications. This retrospective observational case series included all cases who developed massive serofibrinous macular exudation within a week after PDT. Medical records of patients with post-PDT exudative events were reviewed for relevant data and imaging abstraction including optical coherence tomography and indocyanine green angiography features and were subjected to analysis. The incidence rate of PAEM was 4.52%, being noted in 8 eyes (out of 177 PDT sessions in 155 eyes) with a mean age of 70.25 ± 6.65 years. Pre-PDT factors commonly associated with PAEM included age ≥65 years (87.5%), clinical diagnosis of polypoidal choroidal vasculopathy (75%), spot size ≥3,500 µm (100%), best-corrected visual acuity of 20/40 or better (87.5%), low-fluence PDT (87.5%), and the first exposure to PDT (75%). Photodynamic therapy-induced acute exudative maculopathy was noted at a mean interval of 2.9 ± 1.7 days (2-7 days) after PDT. Photodynamic therapy-induced acute exudative maculopathy resulted in significant decrease in mean best-corrected visual acuity from logMAR 0.29 ± 0.21 (approximate Snellen equivalent 20/39) to logMAR 0.91 ± 0.37 (approximate Snellen equivalent 20/163) [P = 0.0018], and significant increase in mean central macular thickness from 228.1 ± 71.8 µm to 481.4 ± 154.8 µm (P = 0.0029). Photodynamic therapy-induced acute exudative maculopathy resolved to baseline or even better tomographic status at a mean interval of 4.6 ± 1.2 weeks, resulting in complete visual recovery compared with baseline. During mean follow-up of 77.8 ± 46.4 weeks after PDT, no activity was noted for a mean duration of 26.3 ± 42.5 weeks after resolution. At final visit, mean best-corrected visual acuity and central macular thickness was logMAR 0.49 ± 0.28 (approximate Snellen equivalent 20/62) and 153.6 ± 40.0 µm, respectively, with underlying pathology being stable in 50% of the eyes. Photodynamic therapy-induced acute exudative maculopathy is an uncommon complication with self-resolving course and favorable prognosis. Patients undergoing PDT should be warned of the possibility of PAEM. The factors frequently associated with PAEM include elderly age (>65 years), clinical diagnosis of polypoidal choroidal vasculopathy, larger spot size (≥3,500 µm), pre-PDT best-corrected visual acuity of 20/40 or better, low-fluence PDT, and the first exposure to PDT.


Electronic Printed Ward Round Proformas: Freeing Up Doctors' Time.
The role of a junior doctor involves preparing for the morning ward round. At a time when there are gaps on rotas and doctors' time is more stretched, this can be a source of significant delay and thus a loss of working time. We therefore looked at ways in which we could make the ward round a more efficient place by introducing specific electronic, printed ward round proformas. We used the average time taken to write proformas per patient and the average time taken per patient on the ward round. This would then enable us to make fair comparisons with future changes that were made using the plan, do, study, and act principles of quality improvement. Our baseline measurement found that the average time taken to write up the proforma for each patient was 1 minute 9 seconds and that the average time taken per patient on the ward round was 8 minutes 30 seconds. With the changes we made during our 3 PDSA cycles and the implementation of an electronic, printed ward round proforma, we found that we were able to reduce the average time spent per patient on the ward round to 6 minutes 32 seconds, an improvement of 1 min 58 seconds per patient. The project has thus enabled us to reduce the time taken per patient during the ward round. This improved efficiency will enable patients to be identified earlier for discharge. It will also aid in freeing up the time of junior doctors, allowing them to complete discharge letters sooner, order investigations earlier and enable them to complete their allocated tasks within contracted hours.


Conformational analysis of mitochondrial and microsomal cytochrome P-450 by resonance Raman spectroscopy.
Mitochondrial and microsomal cytochromes P-450SCC and P-450LM2 in the ferric substrate-free and substrate-bound states were studied by resonance Raman spectroscopy. In the spectra of cytochrome P-450SCC two conformational states (A and B) were detected, each of them constituting an equilibrium between a six-coordinated low-spin and a high-spin form. Both the conformational and the spin equilibria are pH- and temperature-dependent, which is in line with previously published results [Lange, R., Larroque, C., & Anzenbacher, P. (1992) Eur. J. Biochem. 207, 69-73)]. On the basis of well-resolved resonance Raman spectra, measured at different pH and temperatures, these equilibria were analyzed quantitatively. Both low-spin configurations of A and B exhibit different band patterns in the spin state marker band region, indicating differences in the active-site structures. While in the high-spin configuration of state A the heme iron remains weakly bound by a sixth ligand, the high-spin form of state B is five-coordinated. Binding of cholesterol to cytochrome P-450SCC causes a significant population of the high-spin forms, particularly of state A (62%). On the other hand, binding of 22R-hydroxycholesterol to the substrate-free enzyme leaves the overall spin equilibrium largely unchanged, i.e., six-coordinated low spin (76% A and 24% B). In both substrate-bound complexes, interactions between the substrate and the heme lead to small but distinct differences in the resonance Raman spectra of the low-spin form of state A. In contrast to cytochrome P-450SCC, the resonance Raman spectra of microsomal cytochrome P-450LM2 provide no indications for multiple conformers at 22 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)


Age specific mortality trends in the U.S.A. from 1960 to 1980: divergent age-sex-color patterns.
Trends in age-specific mortality (10-year age groups, 5-74) for the U.S. population were reviewed for all causes of death from 1960 to 1980. The age-specific mortality rate generally declined. However, the following age-sex-color groups showed divergent mortality trends compared to those of other groups: (1) The death rates for white male teenagers and young adults (ages 15-24 and 25-34) increased during 1960s and stayed at the same level during 1970s. The ratio of male to female deaths for white teenagers and young adults (15-24 and 25-34) increased over both decades, although the mortality rate for white women age 15-24 increased during the 1960s. (2) Non-white men age 15-24 and 25-34 experienced biphasic mortality trends, with a rise peaking in 1971 and then a fall. (3) The mortality ratios, non-white to white men, age 25-34 and 35-44, were far higher then those of other age groups. (4) The mortality ratios, non-white males to females, increased steadily for all age groups, and those of age groups 15-24 and 25-34 turned up sharply. Selected causes of death (1960-1977) were reviewed to uncover reasons for the unfavorable mortality trends among males. The following causes contributed to rising mortality among males: (a) accidents, suicide, and homicide for white and non-white teenagers and young adults, age 15-24, 25-34 and 35-44; (b) suicide and homicide for non-white men age 45-54; (c) cirrhosis of the liver for white men age 35-44 and for non-white 25-34, 35-44 and 45-54; (d) malignant neoplasms for white men age 35-44 and for non-white age 45-54.


Dynamic detection of ppb-level SO2 based on a differential photoacoustic cell coupled with UV-LED.
We design a photoacoustic (PA) SO2 sensor based on the coupling of a differential photoacoustic cell (DPAC) and cost-effective UV-LED, which realized the dynamic monitoring of SO2 gas at the ppb level. Aiming at the limitation of UV-LED divergence, a light source combination module with high condensing efficiency was devised based on a lens through theoretical derivation and experimental analysis. The PA signal with the optimum matching of the lens was 20-times larger than the direct coupling of the UV-LED. Due to the excellent beam collimation effect of the lens assembly, the background interference was only 1 ppm. In addition, the DPAC gathered the merits of doubling the PA signal and reducing the flow noise interference. The analysis of Allan-Werle deviation showed that the detection limit of SO2 was 1.3 ppb with the averaging time of 100 s.


Molecular Mechanisms Underlying the Acclimation of Chlamydomonas reinhardtii Against Nitric Oxide Stress.
The acclimation mechanism of Chlamydomonas reinhardtii to nitric oxide (NO) was studied by exposure to S-nitroso-N-acetylpenicillamine (SNAP), a NO donor. Treatment with 0.1 or 0.3 mM SNAP transiently inhibited photosynthesis within 1 h, followed by a recovery, while 1.0 mM SNAP treatment caused irreversible photosynthesis inhibition and mortality. The SNAP effects are avoided in the presence of the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl-3-oxide (cPTIO). RNA-seq, qPCR, and biochemical analyses were conducted to decode the metabolic shifts under NO stress by exposure to 0.3 mM SNAP in the presence or absence of 0.4 mM cPTIO. These findings revealed that the acclimation to NO stress comprises a temporally orchestrated implementation of metabolic processes: (1). modulation of NADPH oxidase (respiratory burst oxidase-like 2, RBOL2) and ROS signaling pathways for downstream mechanism regulation, (2). trigger of NO scavenging elements to reduce NO level; (3). prevention of photo-oxidative risk through photosynthesis inhibition and antioxidant defense system induction; (4). acclimation to nitrogen and sulfur shortage; (5). attenuation of transcriptional and translational activity together with degradation of damaged proteins through protein trafficking machinery (ubiquitin, SNARE, and autophagy) and molecular chaperone system for dynamic regulation of protein homeostasis. In addition, the expression of the gene encoding NADPH oxidase, RBOL2, showed a transient increase while that of RBOL1 was slightly decreased after NO challenge. It reflects that NADPH oxidase, a regulator in ROS-mediated signaling pathway, may be involved in the responses of Chlamydomonas to NO stress. In conclusion, our findings provide insight into the molecular events underlying acclimation mechanisms in Chlamydomonas to NO stress.


Association of treatment and outcomes of doctor-shopping behavior in patients with hepatocellular carcinoma.
A variety of unfulfilled needs may trigger doctor-shopping behavior (DSB) in patients. In oncology, treatment results usually cause patients the most concern. This study investigated the association of DSB with active treatments received by patients with hepatocellular carcinoma (HCC) and outcomes. With approval from the institutional review board, all patients registered in the cancer database of a teaching hospital and diagnosed as having HCC by self-referral from outside hospitals or by in-house diagnosis were retrospectively identified. Patient data were then reviewed and analyzed via electronic medical records. Hepatitis B carriers were significantly more likely than noncarriers to show first-time DSB. Recurrent disease was less likely to result in DSB than predicted. Patients from outside hospitals not receiving upfront first treatment after diagnosis were significantly more likely to show more frequent DSB than those receiving it. Male patients eligible for salvage treatment were less likely to have frequent occurrences of DSB than their female counterparts. Receiving first salvage treatment was not associated with more frequent DSB. Treatment recommendations offered in the study hospital did not influence patients' decisions to leave or stay. Only elderly patients (>70 years) were less likely to show DSB. DSB can occur throughout the entire course of treatment for HCC for a variety of reasons. Active treatments, disease status, and patient characteristics all exerted an influence on DSB.


Part 2: Screening, Brief Intervention and Referral to Treatment Plus Recovery Management: A Proposed Model for Recovery-Oriented Primary Care.
Part 1 of this two-part series (The Theoretical Basis for Recovery-Oriented Management of Substance Use Disorders in the Primary Care) explored the theoretical foundations for evidence-based substance Screening, Brief Intervention and Referral to Treatment (SBIRT) services. The aim was to produce possible explanations for why traditional SBIRT works well for individuals with unhealthy alcohol use but not as well for individuals who have more serious substance use disorders, including drug use and alcohol/drug dependence. Building on that analysis, through meaningful application of recovery management (RM) concepts within an integrated primary care/behavioral health context, a new, theory-based, recovery-oriented framework for primary care SBIRT is now introduced in Part 2. The proposed SBIRT Plus Recovery Management (SBIRT + RM) model moves traditional SBIRT from its original, limited, and narrow focus only on substance detection, brief intervention, and referral to its rightful, structured placement within a comprehensive, multidimensional, recovery-oriented system of care clinical practice environment. SBIRT+RM describes relevant strategies for improving recovery outcomes for individuals identified through primary care substance screening and defines primary care provider roles and responsibilities for sustained recovery support and long-term recovery maintenance.


Single reading with computer-aided detection and double reading of screening mammograms in the United Kingdom National Breast Screening Program.
To retrospectively determine if the use of a computer-aided detection (CAD) system can improve the performance of single reading of screening mammograms to match that of double reading in the United Kingdom. Local research ethics committee approval was obtained; informed consent was not required. This study included a sample of 10 267 mammograms obtained in women aged 50 years or older who underwent routine screening at one of two breast screening centers in 1996. Mammograms that were double read in 1996 were randomly allocated to be re-read by eight different radiologists using CAD. The cancer detection and recall rates from double reading and single reading with CAD were compared. Statistical significance and confidence intervals were calculated with the McNemar test to account for the matched nature of the data. Single reading with CAD led to a cancer detection rate that was significantly (P = .02) higher than that achieved with double reading: 6.5% more cancers were detected by means of single reading with CAD than by means of double reading. However, the recall rate was higher for single reading with CAD than for double reading (8.6% vs 6.5%, respectively; P < .001). This was equivalent to relative increases of 15% and 32% in the cancer detection and recall rates, respectively. Single reading with CAD leads to an improved cancer detection rate and an increased recall rate.


Traumatic diaphragmatic rupture with underlying lung laceration and tension pneumoperitoneum.
Tension pneumoperitoneum is commonly caused by gastrointestinal perforation and pulmonary causes are extremely rare. We present a case of a 47-year-old male post motor vehicle accident with a suspected left-sided haemopneumothorax on initial chest x-ray. CT of the chest post chest tube insertion showed a left-sided diaphragmatic rupture and an extensive diaphragmatic hernia. While en-route to the operating theatre, the intubated patient developed tension pneumoperitoneum with positive pressure ventilation and required immediate surgical intervention and repair. A review of the literature around tension pneumoperitoneum and diaphragmatic hernia in trauma is discussed.


An NPPB Promoter Polymorphism Associated With Elevated N-Terminal pro-B-Type Natriuretic Peptide and Lower Blood Pressure, Hypertension, and Mortality.
Elevated B-type natriuretic peptide (BNP) levels are associated with heart failure and increased mortality in the general population. We investigated rs198389, a functional variant in the promoter region of the BNP gene (NPPB), in patients from the Atherosclerosis Risk in Communities Study to investigate associations with N-terminal pro-BNP (NT-proBNP) levels and outcomes. A total of 11 361 black and white patients with rs198389 genotyping attended visit 1 (aged 45-64 years; 1987-1989), with follow-up visits occurring every 3 years (visit 2-visit 4, 1990-1999), followed by visit 5 (2011-2013). NT-proBNP levels were measured at visits 2, 4, and 5. At visit 2, the GG genotype (frequency 18%) was associated with a 41% higher mean plasma level of NT-proBNP compared with the AA genotype (frequency 34%), with intermediate values observed in AGs (P=4.2×10-52). The GG genotype was associated with reduced systolic blood pressure (-1.6 mm Hg, P=0.006), diastolic blood pressure (-1 mm Hg, P=0.003), antihypertension medication use (odds ratio, 0.85; 95% CI, 0.74-0.97 [P=0.02]), and hypertension (odds ratio, 0.81; 95% CI, 0.72-0.92 [P=0.002]) compared with the AA genotype with intermediate values in AGs. These relationships persisted throughout subsequent visits. After a median follow-up of 23 years, there were 4031 deaths. With and without covariate adjustment, the GG genotype was associated with modestly lower mortality (hazard ratio, 0.86; 95% CI, 0.78-0.95), primarily reflective of cardiovascular death (hazard ratio, 0.75; 95% CI, 0.61-0.92), and increased residual lifespan of 8 months from 50 years of age (P=0.02) versus AAs. The rs198389 G allele in the NPPB promoter is associated with elevated levels of NT-proBNP throughout adult life, reduced blood pressure, hypertension and cardiovascular mortality, and increased lifespan.


Night work as a stressor: The role of sleep reactivity to stress in the relationship between night work and insomnia.
Sleep reactivity to stress is a predisposition to experience sleep disturbances in response to stress. The present study aimed to examine the potential moderating role of sleep reactivity to stress in the relationship between the number of night shifts per month as a stressor and insomnia symptoms. A total of 188 shift-working physicians completed a short questionnaire about work schedule, the Ford Insomnia Response to Stress and the Insomnia Severity Index. Sleep reactivity to stress was a significant moderator of the effect of number of nights worked in the last month on insomnia symptoms. At low and medium sleep reactivity to stress the relationship between the number of night shifts per month and insomnia symptoms was positive and significant. At high sleep reactivity to stress the relationship was no longer significant. The results show that with low and medium sleep reactivity to stress, the more night shifts a person works per month, the more severe insomnia symptoms they will report. With high sleep reactivity to stress even a low number of night shifts per month will lead to a deterioration of sleep. This is important for identifying those who are more vulnerable to adverse consequences of working in the shift system, and the knowledge of workers' sleep reactivity to stress may help in providing targeted interventions.


Cross-border movement of older patients: a descriptive study on health service use of Japanese retirees in Thailand.
Thailand's policy to promote long-stay tourism encourages Japanese retirees to relocate to Thailand. One concern of such an influx is the impact of these elderly foreign residents on the Thai health system. This study aims to reveal the current use of and needs for health services amongst Japanese retirees residing in various locations in Thailand. In collaboration with nine Japanese self-help clubs in Bangkok, Chiang Mai, Chiang Rai, and Phuket, questionnaire surveys of Japanese long-stay retirees were conducted from January to March 2015. The inclusion criteria were being ≥ 50 years of age and staying in Thailand for ≥30 days in the previous 12 months while the main exclusion criteria included relocation by company, relocation due to marriage, or working migrants. The mean age of the 237 eligible participants was 68.8, with 79.3% of them being male, 57.8% having stayed in Thailand for ≥5 years, 63.3% having stayed in Thailand for ≥300 days in the previous 12 months and 33% suffering from chronic diseases or sequelae. Of the 143 who had health check-ups in the previous 12 months, 48.3% did so in Thailand. The top 3 diseases treated either in Thailand or Japan in the previous 12 months were dental diseases (50 patients), hypertension (44 patients), and musculoskeletal disorders (41 patients), with the rate of treatment in Thailand standing at 46.0, 47.7, and 65.9%, respectively. Of the 106 who saw a doctor in Thailand in the same period, 70.8% did so less than once a month. Only 23.2% of the participants preferred to receive medical treatment for serious conditions in Thailand. However, this number rose to 32.9% for long-term care (LTC) use. The usage of Thai health services amongst Japanese long-stay retirees is currently limited as they prefer going back to Japan for health screenings and treatment of chronic or serious diseases. However, the number of Japanese residents requiring health services including LTC and end-of-life care is expected to increase. The potential impact of promoting long-stay tourism on the Thai public health should be acknowledged and investigated by the Thai government, including the tourism authority.


Solid-phase synthesis and spectral properties of 2-alkylthio-6H-pyrano[2,3-f]benzimidazole-6-ones: a combinatorial approach for 2-alkylthioimidazocoumarins.
The solid-phase synthesis of 2-alkylthio-6H-pyrano[2,3-f]benzimidazole-6-ones (2-alkylthioimidazocoumarins) is described. 7-Fluoro-4-methyl-6-nitro-2-oxo-2H-1-benzopyran-3-carboxylic acid was coupled to Rink amide resin via its carboxyl group. The resin-bound scaffold then underwent aromatic nucleophilic substitution with primary amines, followed by reduction of the nitro group with tin (II) chloride. Subsequent cyclization of the o-dianilino intermediates with thiocarbonyldiimidazole (TCD) afforded resin-bound 1,3-dihydro-2-thioxo-6H-pyrano[2,3-f]benzimidazole-6-ones, which were then S-alkylated with alkyl halides in the presence of N,N-diisopropylethylamine (DIEA). The desired products were obtained in good yield with high purity after trifluoroacetic acid cleavage. The unique spectral properties of 2-alkylthioimidazocoumarins indicate that they may be useful in photodynamic therapy.


Transauricular vagus nerve stimulation for patients with disorders of consciousness: A randomized controlled clinical trial.
Disorders of consciousness (DoCs) are a frequent complication of brain injury disease, and effective treatments are currently lacking. Transauricular vagus nerve stimulation (tVNS) has been proposed as a promising therapeutic method for neurological disorders such as epilepsy and depression. In our previous study, we demonstrated that vagus nerve stimulation promoted recovery in rats with DoCs caused by traumatic brain injury. However, the clinical effect of vagus nerve stimulation on consciousness disorders is unclear. We aimed to investigate the therapeutic efficacy and safety of tVNS in patients with DoCs. We conducted a randomized, double-blinded, sham-controlled trial. Patients (N = 60) with DoCs, including minimally conscious state (MCS) and vegetative state/unresponsive wakefulness syndrome, were enrolled and randomized to groups receiving either active or sham tVNS. A frequency of 20 Hz and pulse wave of 200 us was used in the active-tVNS protocol, which was performed in the auricular branch of the vagus nerve in the left outer ear. The sham-tVNS protocol was the same as the active-tVNS protocol although without current input. Both groups of patients also received conventional treatments. Consciousness was evaluated according to the Coma Recovery Scale-Revised before and after the 4-week intervention. We also recorded the type and number of behavioral responses. Safety was primarily assessed according to the incidence of treatment-emergent adverse events. Each patient's heart rate and blood pressure were monitored during all treatment sessions. Ultimately, 57 patients completed the study: 28 patients underwent active tVNS and 29 patients underwent sham tVNS. No significant differences were observed in Coma Recovery Scale-Revised scores between the active- and sham-tVNS groups before the tVNS sessions. Compared with patients in the sham-tVNS group (9.28 ± 4.38), patients with DoCs treated with active tVNS showed improved consciousness (10.93 ± 4.99), although not statistically significant. Further analysis revealed obvious differences between patients with MCS receiving active and sham tVNS, but no significant difference in patients with vegetative state/unresponsive wakefulness syndrome in both groups. All side effects were considered common medical conditions with no obvious correlation to tVNS. These preliminary data provide early evidence that tVNS may be an effective and safe approach for promoting the recovery of consciousness, especially in patients with MCS. https://www.chictr.org.cn/edit.aspx?pid=175938&htm=4, identifier: ChiCTR2200066629.


A whole-animal microplate assay for metabolic rate using zebrafish.
Regulation of whole-body metabolism and energy homeostasis has been shown to require signaling between multiple organs. To identify genetic programs that determine metabolic rate, and compounds that can modify it, a whole-animal assay amenable to large-scale screening was developed. The direct correlation of acid production with metabolic rate was exploited to use a noninvasive colorimetric assay for acid secretion by individual zebrafish larvae in a 96-well plate format. A 3-fold increase in metabolic rate was detected that accompanied development between 24 and 96 h postfertilization. Dynamic changes in metabolic rate were also detected in response to different conditions such as temperature and drug treatments, in general agreement with the rate of oxygen consumption measured concomitantly. This assay was used to measure metabolic rate in the progeny of fish known to carry a recessive mutation in a gene required for ribosome biogenesis ( npo(fW07-g)), which would be expected to reduce energy consumption. A strong correlation was found (p < 10(-6) ) between reduced metabolic rate and genotype even before the developmental defect was visually evident. These studies support the conclusion that whole-animal acid secretion can be used as a readout for energy metabolism, thus enabling large-scale screening for genetic and chemical regulators of metabolic rate in a vertebrate.


Castleman's disease, intermediate type: a case report.
Castleman's disease or giant lymph node hyperplasia is a distinct form of lymph node hyperplasia. Histologically, there are 2 variants, hyaline vascular variant which occurs in 90% of the cases and plasma cell type which is rare. We encountered a 70 year old man with Castleman's disease showing intermediate features consisting of both hyaline vascular and plasma cell elements presenting as cervical lymphadenopathy. Following surgical excision, the patient was relieved of his constitutional symptoms and had no recurrence even after 6 months of follow-up.


Effects of release and decompression techniques on nerve roots through percutaneous transforaminal endoscopic discectomy on patients with central lumbar disc herniation.
The clinical effects and safety of release and decompression techniques on nerve roots through percutaneous transforaminal endoscopic discectomy (PTED) while treating patients with central lumbar disc herniation (CLDH) were explored. Patient cases of lumbar and leg pain treated in Bethune International Peace Hospital from July 2013 to October 2015 were collected retrospectively. The patients in these cases received imaging examinations such as computed tomography and magnetic resonance imaging. Among these cases, 37 CLDH patients with no other complications were selected for this study. A total of 22 males and 15 females aged 28-54 years, with an average age of 36.8±1.5 years, were the subjects of the study. Their disease course was from 1 month to 3 years, with a median course time of 1.5 years. Visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) scoring and the MacNab method were used to evaluate treatment effects. After permission from patients or their family members, release and decompression techniques of nerve roots were performed through PTED. All patients had successful surgery. Their average surgery time was 41.3 (25.5-57.1) min. A physician followed-up each patient from 0 to 18 months after surgery, with the average follow-up period of 12.1 months. VAS scoring of lower limbs was 7.95±0.82 before surgery and 2.28±0.35, 3 months after surgery. VAS scoring of lower limbs was 2.06±0.58, 1 year after surgery and 2.12±0.23 at the last follow-up appointment. JOA scoring was 12.6±0.72 before surgery and 20.4±1.08, 3 months after surgery. JOA scoring was 21.1±0.82 1 year after surgery and 21.2±0.36 at the last follow-up. Differences are of statistical significance (P<0.05). There were no complications for any of the cases. One patient did not improve after surgery, so a laminectomy and bone grafting internal fixation were performed. Two patients relapsed after surgery and received laminectomy and bone grafting internal fixation. The total percentage of excellent and good rates was 83.5%. In conclusion, release and decompression techniques on nerve roots using PTED while treating CLDH resulted in a safe, effective and less traumatic outcome with fewer complications and quicker pain relief than alternative treatments. Due to the results of this study, the use of these techniques in treating CLDH should be more widely considered.


Case Series of Comminuted Olecranon Fracture Treated by Plate Fixation; Do We Have to Remove the Plate?
Comminuted olecranon fracture requires surgical intervention. Plate fixation has been performed on the majority of cases. We reviewed the cases of comminuted olecranon fracture in young and middle age treated by plate osteosynthesis and analyzed the functional outcome, complications and ratio and timing of hardware removal. Fifteen cases of comminuted olecranon fractures treated by plate fixation were reviewed. Bone union was achieved in all cases, the average range of motion at the final follow up was -11° in extension, 133° in flexion, 89° in pronation and 88° in supination. Hardware removal performed in 12 cases in average 8.3 months postoperatively, in 2 cases elbow joint contracture release was performed during the hardware removal. In the co-payment (+) group, 4 cases (67%) removed the plate at average six months postoperatively. On the other hand, no co-payment group (workman's compensation insurance or automobile liability insurance) underwent hardware removal surgery in 8 cases (89%) at 9.6 months postoperatively. There was no statistical difference between the timing or prevalence of hardware removal between the groups. The present study showed high removal rate of hardware despite the excellent clinical result. The surgeons should be aware that plate fixation of the olecranon fracture requires the removal of a plate in the majority of cases.


Circumscribed shapes are enlarged: is this a variation of the Delboeuf illusion?
Pairs of complex shapes, for example, two golf holes or two hands making a peace sign, were printed on cards with one of the two shapes surrounded by a circle. 20 participants judged the size of the unenclosed shapes relative to the size of the enclosed ones. For 12 pairs in which there were physical differences in size of the two shapes, participants made veridical judgments. More importantly, for the six pairs in which the unenclosed and circumscribed shapes were the same size, the unenclosed shapes were judged smaller than the circumscribed ones. Thus, a novel illusion in which surrounding circles perceptually enlarge a variety of interior shapes is demonstrated.


Granuphilin molecularly docks insulin granules to the fusion machinery.
The Rab27a effector granuphilin is specifically localized on insulin granules and is involved in their exocytosis. Here we show that the number of insulin granules morphologically docked to the plasma membrane is markedly reduced in granuphilin-deficient beta cells. Surprisingly, despite the docking defect, the exocytosis of insulin granules in response to a physiological glucose stimulus is significantly augmented, which results in increased glucose tolerance in granuphilin-null mice. The enhanced secretion in mutant beta cells is correlated with a decrease in the formation of the fusion-incompetent syntaxin-1a-Munc18-1 complex, with which granuphilin normally interacts. Furthermore, in contrast to wild-type granuphilin, its mutant that is defective in binding to syntaxin-1a fails to restore granule docking or the protein level of syntaxin-1a in granuphilin-null beta cells. Thus, granuphilin not only is essential for the docking of insulin granules but simultaneously imposes a fusion constraint on them through an interaction with the syntaxin-1a fusion machinery. These findings provide a novel paradigm for the docking machinery in regulated exocytosis.


Management of neonatal sepsis by Gram-negative pathogens.
For the pediatrician and neonatologist who care for term and preterm infants, the challenge remains to keep these infants free of infection after delivery in special-care nurseries and neonatal intensive care units. Studies of complications associated with term infants at risk due to maternal factors, as well as preterm infants after early delivery, have demonstrated that sepsis is a major cause of neonatal mortality and morbidity. Infections due to Gram-negative organisms are increasingly being reported from neonatal units. Moreover, Gram-negative organisms that are multidrug resistant are on the increase and pose a formidable clinical challenge. In this article, we review current epidemiology, risk factors, clinical features, diagnosis, therapy and preventive measures related to Gram-negative infections in neonates.


Healthcare Professionals, Post-traumatic Stress Disorder, and COVID-19: A Review of the Literature.
The recent COVID-19 pandemic impacted healthcare professionals psychologically. They were unprepared to handle such a powerful and unknown virus. Consequently, they had to face situations of extreme distress, developing vicarious traumatization and post-traumatic stress disorder (PTSD). The first one is associated with the "cost of caring" for others and affected persons who constantly are exposed to other sufferings. PTSD is a psychiatric disorder that could affect people who have experienced or witnessed a traumatic event. Post-traumatic stress disorder (PTSD) and correlated symptoms might impact the lives of healthcare professionals at the personal, professional, and relational levels. Furthermore, the pandemic could decrease the empathy of healthcare professionals, influencing their relationship with patients. This review aimed to describe the incidence of PTSD among HPs during the COVID-19 pandemic. We focused on the following aspects: (a) PTSD symptoms and correlated psychological issues, (b) repercussions at working and personal levels, (c) change in empathetic involvement of healthcare professionals.


Use of monoclonal antibodies in immunocytochemical localization of estrogen receptors in ovarian cancer.
Ovarian cancer specimens from 45 patients were assayed for the presence of estrogen receptor (ER) utilizing highly specific monoclonal antiestrophilin antibodies and the peroxidase-antiperoxidase technique. Results were compared with the conventional ER determination of the dextran charcoal method (DCC) and were in concordance in 91% of cases. This technique was also used to analyze ER in fine needle aspiration biopsy specimen from four patients with metastatic ovarian tumor. These results suggest that antireceptor monoclonal antibody in immunohistochemical analysis is an effective tool in the evaluation of estrogen receptor content in ovarian cancer. This technique can be easily performed at community hospitals and may be extended to the evaluation of fine needle aspiration biopsies and to analyze specimens of insufficient size for biochemical assay.


Nanohybrids from direct chemical self-assembly of poly(styrene-alt-maleic anhydride) as pH-responsive particulate emulsifiers.
The nanohybrid particulate emulsifiers based on poly(styrene-alt-maleic anhydride) (SMA) were facilely prepared via the direct chemical self-assembly triggered by the aminolysis of SMA with 3-aminopropyltriethoxysilane (APTES) and the in situ polycondensation of APTES under refluxing in acetone. Transmission electron microscopy and scanning electron microscopy confirmed the spherical-like morphology of the nanohybrids. Dynamic light scattering and electrophoresis revealed the structure transition of the nanohybrids in response to pH change. The emulsification study showed that the nanohybrids were effective particulate emulsifiers when homogenized with various oils including toluene, paraffin oil, silicone oil, isooctyl palmitate, dicaprylyl carbonate, and propylheptyl caprylate. The nanohybrid particulate emulsifiers exhibited pH-sensitivity, and the diameter of paraffin oil droplets remarkably increased with pH of the nanohybrid aqueous dispersion decrease. Also, the reduced dynamic interfacial tension predicted the thermodynamically unstable state of the emulsions prepared at high pH values. Most interesting, the paraffin oil-in-water high internal phase emulsions (HIPEs) with a high oil volume fraction of 83.3% were formed when the nanohybrids were heavily flocculated by adding HCl. The HIPEs were pH-responsive and capable of demulsification with the addition of an alkaline solution showing a potential application in the oil industry.


Precision Heart Rate Estimation Using a PPG Sensor Patch Equipped with New Algorithms of Pre-Quality Checking and Hankel Decomposition.
A new method for accurately estimating heart rates based on a single photoplethysmography (PPG) signal and accelerations is proposed in this study, considering motion artifacts due to subjects' hand motions and walking. The method comprises two sub-algorithms: pre-quality checking and motion artifact removal (MAR) via Hankel decomposition. PPGs and accelerations were collected using a wearable device equipped with a PPG sensor patch and a 3-axis accelerometer. The motion artifacts caused by hand movements and walking were effectively mitigated by the two aforementioned sub-algorithms. The first sub-algorithm utilized a new quality-assessment criterion to identify highly noise-contaminated PPG signals and exclude them from subsequent processing. The second sub-algorithm employed the Hankel matrix and singular value decomposition (SVD) to effectively identify, decompose, and remove motion artifacts. Experimental data collected during hand-moving and walking were considered for evaluation. The performance of the proposed algorithms was assessed using the datasets from the IEEE Signal Processing Cup 2015. The obtained results demonstrated an average error of merely 0.7345 ± 8.1129 beats per minute (bpm) and a mean absolute error of 1.86 bpm for walking, making it the second most accurate method to date that employs a single PPG and a 3-axis accelerometer. The proposed method also achieved the best accuracy of 3.78 bpm in mean absolute errors among all previously reported studies for hand-moving scenarios.


The purified alpha subunits of Go and Gi from bovine brain require beta gamma for association with phospholipid vesicles.
The purified G-proteins from bovine brain were examined for potential solubility in the absence of detergent. The isolated alpha o and alpha i subunits migrated through sucrose with rates consistent with the existence of monomeric species either in the presence or the absence of cholate. The beta gamma subunits or holo-G-proteins aggregated extensively if cholate was absent. Al3+, Mg2+, and F- prevented the aggregation of alpha o and alpha i caused by the addition of beta gamma and could also prevent the aggregation of alpha s when Gs was examined at higher temperature. The association of subunits with phospholipid vesicles was examined. Whereas beta gamma associated totally with phospholipid vesicles, purified alpha o showed little interaction. alpha o did bind to vesicles containing beta gamma (beta gamma vesicles) in a saturable fashion that indicated a stoichiometric association between the subunits. Treatment with guanosine 5'-(3-O-thio)triphosphate could partially dissociate alpha o that was bound to beta gamma vesicles. These data suggest that beta gamma may be an anchor for association of alpha subunits with membranes and that regulation by these proteins may not be limited to the plasma membrane. This possibility and its implications are discussed. The reversible association of alpha o to beta gamma vesicles may provide a very sensitive system for the study of the interactions between these subunits.